Nevirapine safe and effective in patients with a CD4 cell count below 200

Nevirapine-containing HAART regimens are effective and safe in HIV-positive patients with severe immune suppression, according to a retrospective Spanish study published in the August 20^th edition of AIDS. Although only 43% of patients in the rigorous intent-to-treat analysis remained on nevirapine and had suppressed viral load after two years, the investigators emphasise that this was due to poor adherence rather than a lack of drug potency or discontinuation due to treatment side-effects.

The data are likely to reassure clinicians prescribing antiretroviral therapy in resource-limited settings, where the vast majority of patients will begin treatment with CD4 cell counts below 200 cells/mm³. In Europe and North America it is recommended that people with HIV should begin treatment before the CD4 cell count falls below 200 cells/mm³ in order to reduce the risk of developing opportunistic infections. People who begin treatment after the CD4 cell count has fallen below 200 cells/mm³ often have undiagnosed HIV infection that becomes evident only when they are hospitalised with serious opportunistic infections.

Non-nucleoside-based regimens have become the preferred first-choice HAART regimen due to their potency, tolerability and ease of dosing. However, there are few studies that have looked at their efficacy and safety in patients with advanced immune suppression. There have been concerns that nevirapine in particular would lack the potency to achieve good virological suppression in patients with advanced HIV disease. In addition, concerns have been expressed about the potential for nevirapine to cause liver toxicities.

Spanish investigators conducted a retrospective review of the medical records of 118 HIV-positive patients with a CD4 cell below 200 cells/mm³ who started a nevirapine-containing HAART regimen between 1999 and 2002. Patients were followed-up for two years and the study end-point was the proportion of patients with a viral load below 50 copies/ml at this point. The investigators conducted both intent-to-treat analysis and on-treatment analyses.

Almost half the individuals enrolled in the study (49.2%) had acquired HIV from injecting drug use, and were also infected with hepatitis C virus. The median viral load at baseline was a little over 80,000 copies/ml and the median CD4 cell count was 105 cells/mm³In total, 47% of patients had a CD4 cell count below 100 cells/mm³ and 20% had a viral load above 300,000 copies/ml. An abnormal liver function was present in 11% of individuals at baseline.

In the intent-to-treat analysis, 54% of patients had a viral load of less than 50 copies/ml after a year of follow-up and 43% after 24 months. Viral load at baseline did not affect the chances of achieving an undetectable viral load.

CD4 cell count increased by a mean of 156 cells/mm³ at month twelve and 235 cells/mm³ at month 24. After two years of treatment, 83% of patients had a CD4 cell count above 200 cells/mm³ and 98% a CD4 cell count above 100 cells/mm³.

There were no HIV-related deaths during the study, although two patients experienced new AIDS-defining illnesses: one case of cytomegalovirus (CMV) retinitis, and a case of Pneumocystis pneumonia (PCP). Interestingly, both patients had relatively high CD4 cell counts, the CMV occurring six months after commencing therapy in an individual whose CD4 cell count was above 300 cells/mm³ by this point.

A total of 50 patients stopped taking nevirapine before the end of the two years of follow-up. The most common reason was poor adherence (23 individuals). Virological failure was observed in eleven patients, and ten patients stopped taking the drug because of side-effects.

Of the patients who stopped nevirapine because of toxicities, six did so because of liver problems and two because of rash. The presence of elevated alanine aminotransferase (ALT) values at baseline was significantly associated with liver toxicity during nevirapine treatment (p = 0.005).

“In this cohort, 83% of patients who continued with nevirapine and tolerated it after 24 months had a HIV [viral load] less than 50 copies/ml and CD4 cells greater than 200 cells/mm³” comment the investigators when presenting the on-treatment data. They add, “the high proportion of patients who did not adhere to therapy or were lost to follow-up (above 20%) contributed to the relatively low efficacy rate shown by the intent-to-treat analysis at 24 months. This highlights the importance, in the ‘real-world’, of reinforcing adherence to therapy and attending clinic visits even in patients receiving ‘simple’ regimens.”

Although approximately 50% of patients started treatment with a CD4 cell below 100 cells/mm³, the mean CD4 cell count after 24 months was 342 cells/mm³ and only two new AIDS-defining events were recorded.

The investigators add that the risk of side-effects did not appear to be any higher in patients with advanced immune suppression, and emphasise that an abnormal baseline ALT value predisposed individuals to a higher risk of toxicities.

“Nevirapine regimens may play a role even in immunosuppressed HIV-infected naïve patients who do not tolerate more complex or potent regimens,” conclude the investigators.